Sorbent and chemical regeneration of dialysate

ABSTRACT

The present invention generally relates to systems and methods for the regeneration of spent dialysis solutions. The present invention further relates to systems and methods for continuously regenerating spent dialysis solution during dialysis. The present invention further relates to systems and methods for conducting dialysis that further include using chemical and physical separators in conjunction with ion exchange cartridges and/or adsorption cartridges.

This application is a divisional of U.S. patent application Ser. No.14/237,896, filed Feb. 10, 2014, which in turn is a National StageApplication of PCT/US2012/051246, filed Aug. 17, 2012, which claims thebenefit under 35 U.S.C. §119(e) of prior U.S. Provisional PatentApplication No. 61/524,793, filed Aug. 18, 2011, which is incorporatedin its entirety by reference herein.

BACKGROUND OF THE INVENTION

Dialysis is a treatment that removes waste products, toxins such asurea, creatinine, and uric acid, and excess fluid that accumulate in thebody's blood and tissues as a result of kidney failure or kidneydysfunction. Dialysis treatment is critical for a person, who has kidneyfailure or reduced kidney function, because a person cannot continue tolive without the filtration functions provided by the kidneys.

Hemodialysis is one type of dialysis treatment where toxins are filteredfrom a patient's blood extracorporeally using a hemodialysis machine.The hemodialysis machine generally contains a computer, fluid pumps,blood lines, dialysate lines, a dialyzer, and drain lines for discardingthe large volumes of dialysis solution used in each treatment. Thepatient's circulatory system is connected to a hemodialysis machine viacatheters or fistula needles and the patient's blood is pumpedcontinuously through the hemodialysis machine. The blood passes througha dialyzer containing semi-permeable membranes in the hemodialysismachine. The semi-permeable membranes separate the blood on one sidefrom dialysis solution on the other side. The dialyzer removes thewaste, toxins and excess water from the blood, and then returns theblood to be re-infused in the patient. The waste products and toxinstransfer out of the blood through the semi-permeable membrane into thedialysis solution, which is then discarded. A large amount of dialysate,i.e., approximately 90-120 liters, is used by most hemodialysis machinesduring a single dialysis treatment. The used or spent dialysate is thendiscarded. Hemodialysis treatments typically are conducted three or fourtimes a week at service centers under the supervision of clinicians.Each treatment takes approximately four to six hours and requires alarge supply of dialysis solution or a continuous source of water. Thespent dialysate is typically discarded.

Peritoneal dialysis is another type of dialysis treatment where toxinsand excess water are filtered from a patient's blood and organs byintroducing dialysis solution containing glucose or dextrose and otherelectrolytes into the peritoneal cavity allowing the dialysis solutionto dwell for a period of time. The abdominal cavity has an exceptionalblood supply where urea and other toxins in the blood transfer to thedialysis solution. Patients either use pre-prepared dialysis solution orprepare the dialysis solution using purified water from their home.Peritoneal dialysis treatments typically are conducted at the patient'shome on a daily basis and require 10-15 liters of dialysate pertreatment. The spent dialysate is typically discarded.

Continuous Ambulatory Peritoneal Dialysis (CAPD) and Continuous CyclingPeritoneal Dialysis (CCPD) are two types of peritoneal dialysis thatallow the dialysis solution to dwell in the peritoneum for a period oftime. During CAPD and CCPD, dialysis solution is introduced into theperitoneum and, after a period of time, the dialysis solution is drainedand discarded. Then, new dialysis solution is introduced into theperitoneum. During each treatment, the fill, drain and dwell sequence isrepeated as prescribed. In CAPD, the filling, dwelling and draining aredone manually. In CCPD, the filling, dwelling and draining is done by amachine.

Another type of peritoneal dialysis is Continuous Flow PeritonealDialysis (CFPD). During CFPD, dialysis solution is introduced into theperitoneum using two separate catheters or a double lumen catheterthrough the inflow catheter while the outflow catheter is clamped. Oncethe desired fill volume is achieved, the outflow catheter is opened, andthe inflow and outflow flow rates are maintained relatively constant sothat the dialysis solution is continuously pumped through theperitoneum. CFPD is typically performed at high flow rates and requiresvery large volumes of dialysis solution.

The use of certain devices to regenerate spent dialysis solution fromhemodialysis and/or peritoneal dialysis is known in the art. Forexample, the Redy™ (REcirculating DYalysis) Sorbent System (Blumenkrantzet al., Artif Organs 3(3):230-236, 1978) includes a sorbent cartridgewith multiple layers for removing toxins and other waste products fromdialysis solution. Sorbent cartridges require a significant amount ofmaterial and layers. Almost half of the material in the cartridge iszirconium phosphate, which binds and removes ammonia.

A need exists to provide improved dialysis systems. This can beaccomplished by reducing the amount of water or dialysis solution neededfor each treatment and by reducing the amount of sorbent material neededfor each treatment. Each dialysis treatment requires a large supply ofdialysis solution or a continuous source of water. A patient undergoinghemodialysis three times a week requires approximately 270-360 liters ofdialysate a week. A patient undergoing peritoneal dialysis requiresapproximately 70-105 liters per week.

SUMMARY OF THE PRESENT INVENTION

The present invention provides systems and methods for the regenerationof used dialysis solution also known as dialysate. The dialysateregeneration system can be integrated into any dialysis system thatrequires the use of dialysate.

In one aspect of the invention, a dialysis system incorporates a sorbentdevice configured to allow dialysis solution to pass through, anextractor, and a fluid line in fluid communication with the device andextractor. The device is adapted to remove one or more substances fromthe dialysis solution as the dialysis solution passes through thedevice. The extractor is adapted to remove one or more substances fromthe dialysis solution as the dialysis solution passes through theextractor.

The device can be one or more sorbent cartridges. The sorbentcartridge(s) can include at least one layer (or otherwise be present inthe cartridge) of material capable of purifying water and/or spentdialysis solution. A layer of the sorbent cartridge can comprise jackbean meal, encapsulated jack bean meal, cross-linked jack bean meal orother stabilized urease, or any combination thereof. One or more of thesorbent cartridge(s) can additionally comprise a layer of hydrouszirconium oxide, an anion exchange resin, or activated carbon, or anycombination thereof. The one or more sorbent cartridge(s) can compriseone or more of these layers. The one or more sorbent cartridge(s) cancontain more than one compartment.

The regeneration system can further include a second device. The seconddevice can be one or more sorbent cartridge(s). The second sorbentcartridge can comprise hydrous zirconium oxide or an anion exchangeresin or any combination thereof, such as in the form of one or morelayers. A layer of the second sorbent cartridge can comprise activatedcarbon. The second sorbent cartridge can contain more than onecompartment.

The extractor system can comprise a liquid-liquid countercurrentextractor that complexes ammonia in the dialysate to an extractingmolecule in the extracting fluid. The extracting molecule can be aphosphinic acid, a carboxylic acid, or a phosphoric acid, or anycombinations thereof. The extracting fluid can be Norpar 12, undecane, avegetable oil, a modified vegetable oil or a biodiesel. The extractingfluid can be a biodiesel containing dissolved di-2,4,4-trimethylpentylphosphinic acid.

Other aspects, features and advantages of the present invention will beapparent from the claims.

Additional features and advantages of the present invention will be setforth in part in the description that follows, and in part will beapparent from the description, or may be learned by practice of thepresent invention. The objectives and other advantages of the presentinvention will be realized and attained by means of the elements andcombinations particularly pointed out in the description and appendedclaims.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are intended to provide a further explanation of the presentinvention, as claimed.

The accompanying drawings, which are incorporated in and constitute apart of this application, illustrate some of the features of the presentinvention and together with the description, serve to explain theprinciples of the present invention.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic of a hemodialysis system according to an exampleof the present application. Reference characters are shown in FIG. 1which refer to the following:

-   -   100—An Example of the Regeneration System of the Present        Invention    -   101—Spent Dialysate    -   102—Sorbent Cartridge for Hydrolyzing Urea    -   103—Liquid-Liquid Countercurrent Separator    -   104—Ammonia Complexed to Extracting Fluid    -   105—Heat Cycler    -   106—Regenerated Extractant Fluid    -   107—Expelled Ammonia    -   108—Sorbent Cartridge for Removing Phosphorous and Organic        Uremic Toxins    -   109—Regenerated Dialysate    -   110—Extractor System    -   111—Dialyzer    -   112—Blood Inlet    -   113—Blood Outlet    -   114—Patient    -   115—Regenerated Dialysate Inlet    -   116—Spent Dialysate Outlet.

FIG. 2 is a schematic of a peritoneal dialysis system according to anexample of the present application. Reference characters are shown inFIG. 2 which refer to the following:

-   -   200—An Example of the Regeneration System of the Present        Invention    -   201—Spent Dialysate    -   202—Sorbent Cartridge for Hydrolyzing Urea and Removing        Phosphorous and Organic Uremic Toxins    -   203—Liquid-Liquid Countercurrent Separator    -   204—Ammonia Complexed to Extracting Fluid    -   205—Heat Cycler    -   206—Regenerated Extractant Fluid    -   207—Expelled Ammonia    -   208—Regenerated Dialysate    -   209—Extractor System    -   210—Patient    -   211—Patient Catheter    -   212—Dialysate Bag.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

The present invention relates to dialysis systems and methods, whichinclude a module for regenerating spent dialysate. The module removesurea, phosphate, and other organic uremic toxins from spent dialysateusing one or more sorbent cartridges and a liquid-liquid counter currentextractor. As described in more detail below, the present invention isuseful in regenerating dialysate used in hemodialysis and peritonealdialysis. The present invention can be used to continuously regeneratedialysate during dialysis treatment or to regenerate dialysate afterdialysis for future use. For the purposes of the present disclosure,dialysate means dialysis solutions useful in hemodialysis or peritonealdialysis systems.

The systems and methods described herein can advantageously reduce thecosts associated with dialysis by reducing the amount of sorbent and/ordialysate (or water) used during each dialysis treatment. Anotheradvantage is that the amount of product and packaging waste producedduring each dialysis treatment can be reduced because the systems andmethods use smaller cartridges and/or smaller volumes of dialysate (orwater).

The spent dialysate can be sent through a cartridge containing a sourceof urease. As an option, the spent dialysate can be sent through acartridge containing jack bean meal, encapsulated jack bean meal,cross-linked jack bean meal or other stabilized urease, or anycombination thereof, and can be in the form of one or more layers orotherwise present in the cartridge, to hydrolyze the urea to ammonia andcarbon dioxide, or ammonium carbonate, or other hydrolytic conversionsof the urea to ammonia. The dialysate containing ammonia is then treatedby a liquid-liquid countercurrent extractor to remove the ammonia. Theextractor contains an extracting liquid(s) that is immiscible withammonia containing dialysate. The extracting liquid contains anextractant, such as di-2,4,4-trimethylpentyl phosphinic acid, that bindsammonia and removes the ammonia (e.g., entirely, almost entirely,substantially, or at least a portion thereof, such as removing from 95%to 100% by weight, or 96% to 100% by weight, or 97% to 100% by weight,or 97% to 99.9% by weight of all ammonia present) from the spentdialysate. Then, the spent dialysate can be sent through a secondcartridge, for instance, one containing hydrous zirconium oxide (HZO)and/or anion exchange resin to remove phosphate. HZO can have theformula ZrO₂.nH₂O (e.g., zirconium oxide hydrate) or ZrO₂.nOH H⁺An⁻ inthe anion form where An is an anion attached to HZO, such as acetate, orchloride, and the like. Without the anion, it can be considered aspartially oxolated zirconium hydroxide with various degrees of O²⁻, OH⁻and H₂O bonded to Zr, i.e., Zr(OH)_(x)O_(y)(H₂O)_(z). The secondcartridge may alternatively contain activated carbon to remove organicuremic toxins or the activated carbon may be housed in a thirdcartridge. After passing through the final cartridge, the regenerateddialysate is ready for reuse. The second cartridge can contain both theHZO or anion exchange resin and the activated carbon in separate layersor multiple layers.

As used herein, “ammonia” refers to at least one of non-ionic ammonia(NH₃) and ammonium ion (NH₄ ⁺) in any form including ammonium hydroxide(NH₄ ⁺OH⁻) or ammonium salt, such as ammonium carbonate ((NH₄ ⁺)₂CO₃⁻²), ammonium bicarbonate (NH₄ ⁺HCO₃ ⁻) and ammonium chloride (NH₄⁺Cl⁻).

FIG. 1 shows an illustrative hemodialysis system that includes anexample of the present invention 100. A hemodialysis machine likeFresenius 2008T, which is not shown, controls the flow rates of theblood and dialysate and monitors the dialysis process. Patient 114 iscoupled to hemodialyzer 111 via bloodlines 112, 113. Blood flows frompatient 114 using a catheter or any other suitable blood access deviceto the dialyzer 111 through the blood inlet 112 and exits through theblood outlet 113. Clean blood is returned to the patient. Cleandialysate flows to the dialyzer 111 through the dialysate inlet 115 andexits through the dialysate outlet 116. As shown by the directionalarrows, the blood flows countercurrent to the dialysate. The blood flowand dialysate flow in the dialyzer can be swapped such that the bloodflows top-to-bottom and the dialysate flows bottom-to-top. Spentdialysate 101 is sent through a cartridge 102 containing material tohydrolyze urea to ammonia or ammonium carbonate. Spent dialysate 101 isthen treated by an extractor system 110 to remove ammonia. The extractorsystem 110 is a liquid-liquid countercurrent extractor 103 and a heatexchanger or heat cycler 105. The extractor 103 uses a solventcontaining a dissolved extracting molecule to remove the ammonia fromthe spent dialysate. The extracting molecule binds or complexes theammonia. The heat cycler 105 heats the solvent containing the extractingmolecule complexed to the ammonia and breaks the complex to release theextracting molecule and the ammonia. The temperature provided by theheat cycler can be 100° C. or higher, such as 125° C. or higher (e.g.,100° C.-170° C., 100° C.-150° C., or 110° C.-150° C., or 115° C.-150°C.). Essentially, the heat provided is such that the extracting moleculereleases the ammonia. The recycled extracting molecule and solvent canbe returned to the extractor 103 to be reused. Spent dialysate 101 exitsthe extractor system 110 and can be sent through a cartridge 108containing material to remove phosphate and/or other organic uremictoxins. Regenerated dialysate 109 can be returned to the dialyzer 111 tocontinue dialysis treatment.

The cartridge 102 includes a housing containing any suitable amount andtype of material to effectively hydrolyze urea in the dialysate toammonia as it flows along the fluid path. The material can be disposablesuch that after use, the material can be removed from the housing andreplaced with new material. The material can be regenerated, such thatafter use, it can be processed for reuse. The material can be jack beanmeal, encapsulated jack bean meal, cross-linked jack bean meal, alumina(aluminum oxide) with jack bean meal, or other stabilized urease, or anycombination thereof.

The cartridge 108 includes a housing containing any suitable amount andtype of material to effectively remove phosphate and other organicuremic toxins in the dialysate as it flows along the fluid path. Thematerial can be disposable such that after use, the material can beremoved from the housing and replaced with new material. The materialcan be one or more materials selected from activated carbon, zirconiumoxide, and/or hydrous zirconium oxide. The material can be hydrouszirconium oxide and activated carbon. The material to remove phosphatecan be an anion exchange resin. The anion exchange resin can beregenerated, such that after use, it can be processed for reuse.

The cartridges 102, 108 can be arranged in series or can be combinedinto one cartridge. The cartridges and/or the materials contained in thecartridges can be arranged in any way such that the urea in the dialysissolution is hydrolyzed to ammonia prior to the extractor system.

The extractor system 110 includes a liquid-liquid countercurrentextractor 103 and a heat cycler 105. Liquid-liquid extraction, alsoknown as solvent extraction, is an extraction of a substance from oneliquid phase into another liquid phase of two different immiscibleliquids. The liquids are usually water and an organic solvent. Theextraction system can comprise one or two or more extractorcompartments. The spent dialysate can pass through multiple compartments(if used) in a sequential manner. If multiple compartments are used, thesolvent and/or extractor molecule can be the same or different. Thesolvent and extractor molecule are separated from the spent dialysatedue to the immiscible properties such that one can be removed from thetop of the compartment or bottom due to the specific gravity of theliquid.

In the present invention, the liquid-liquid countercurrent extractor 103includes two immiscible liquids and an extractor molecule tocontinuously remove ammonia from the spent dialysate 101. One of theliquids in the extractor 103 is the spent dialysate 101 and the otherliquid is a solvent containing an extractor molecule. The spentdialysate 101 is purified water with dissolved water soluble salts. Thespent dialysate 101 may additionally contain an osmotic agent, such assucrose or glucose.

The extractor molecule can be one or more cation exchange moleculesdissolved in the solvent. The extractor molecule binds with ammonia toform a complex and remove ammonia from the spent dialysate 101. Thesolvent with the complexed ammonia 104 is heated by the heat cycler 105to break the complex, expel the ammonia and regenerate the extractormolecule in the solvent. The solvent containing the extractor molecule106 can be returned to the liquid-liquid countercurrent extractor 103 tocontinue removing ammonia from the spent dialysate 101. The expelledammonia 107 can be captured for disposal or used for other purposes,such as for commercial use.

The extractor molecule can have the characteristics of forming an ionpair with the ammonium ion and of decomposing the ion pair thermally torelease ammonia. The extractor molecule can be thermally stable at thetemperature required to carry out the removal of ammonia and theregeneration of the extractor molecule. The extractor molecule candissolve in the solvent, can be more likely to bind to ammonia overother cations, can be readily recovered after thermally releasingammonia, and/or can have pKa values of about 3 to 7. The extractormolecule can be or include a phosphinic acid, a carboxylic acid, or aphosphoric acid, or any combination thereof.

The extractor molecule can be or include a dialkyl phosphinic acid, suchas di-2,4,4-trimethylpentyl phosphinic acid. The use ofdi-2,4,4-trimethylpentyl phosphinic acid as a liquid cation exchanger toremove ammonia from wastewaters in the combined stripping/extractionprocess is disclosed in: Poole, L. J. (2008), “Novel Regenerated SolventExtraction Processes for the Recovery of Carboxylic Acids or Ammoniafrom Aqueous Solutions Part II. Recovery of Ammonia from Sour Waters,”Lawrence Berkley National Laboratory, LBNL Paper LBL-28615. Retrievedfrom: http://escholarship.org/uc/item/2rc4q0b2, incorporated in itsentirety by reference herein.

The extractor molecule can be or include an alpha, alpha, di-substitutedmoderate chain length carboxylic acid. The di-substituted portion of thecarboxylic acid is strongly electron withdrawing and is substituted withelements such as chlorine or fluorine. The alpha carbon refers to thefirst carbon that attaches to the carboxyl group. Alpha, alpha,di-substituted refers to the alpha carbon or the carbon closest to thecarboxyl group having two substituted atoms such that two fluorine atomsor two chlorine atoms are bound to the alpha carbon. These substitutionsmake the carboxylic acid more acidic.

The extractor molecule can be or include dialkyl phosphoric acid havingthe following chemical structure:

The R group is any sufficiently large water repellant group that makesthe phosphoric acid oil soluble. The R group can have 8 to 20 carbonatoms. The R group can be a straight chain, aromatic ring, or alkylring, including, but not limited to, naphthyl, cyclohexyl, a benzylgroup, or a phenyl group. Each R group can be the same or different fromeach other in the above chemical structure.

The solvent in the extractor 103 can be undecane, Norpar 12, a vegetableoil, a modified vegetable oil, a biodiesel, or any combination thereof.The solvent can be, for example, a modified vegetable oil or abiodiesel. Modified vegetable oils and biodiesels are well-knownproducts and readily available commercially. Vegetable oils containtriglycerides which are three fatty acids esterified to glycerol. Toconvert the vegetable oil to a biodiesel, the material can betransesterified to produce a lower viscosity liquid. A modifiedvegetable oil can be transesterified di- and tri-glycerides.Transesterification occurs when di- and tri-glycerides are reacted withethanol and methanol. The modified vegetable oil can reduce theviscosity of the original vegetable oil and can improve its functioningas a solvent and phase separator from the dialysate. A biodiesel can bea material made from vegetable oils or animal fats. All biodiesels aretriglycerides, three fatty acids bound by glycerol. The manufacture ofbiodiesels with improved characteristics is well-known. For example,U.S. Pat. No. 6,583,302, incorporated in its entirety by referenceherein, describes preparing triglyceride oils having unsaturated fattyacid substituents from vegetable oils. The resulting triglyceride oilscan have improved thermal and/or oxidative stability, and/or can havelow temperature performance properties and/or can beenvironmentally-friendly. Further examples of biodiesels are describedin U.S. Pat. Nos. 6,015,440; 6,235,104; 7,918,905; and 7,101,519, allincorporated in their entirety by reference herein.

The solvent of the present invention can have one or more of thefollowing properties or characteristics: water insoluble; thermallystable; oxidatively stable; low viscosity; and/or low density. Thesolvent can have at least two, at least three, or at least four of theabove characteristics. The solvent can have all of the abovecharacteristics. The solvent can have a water solubility range at orbelow about 100 ppm water. The solvent can have a density of about 0.70to 0.95 kg/L, such as about 0.7 to 0.8 kg/L. The solvent can have aviscosity of about 2 to 30 cSt, such as about 2 to 20 cSt. The solventcan have a melting point at or below about 20° C., and/or a boilingpoint at or above about 130° C., and/or a flash point at or above about130° C. The solvent can be non-toxic and/or biocompatible. The solventcan be capable of readily dissolving the extractor molecule and/or canbe fairly immiscible or fully immiscible with water.

FIG. 2 shows an illustrative peritoneal dialysis system that includes anexample of the present invention 200. A peritoneal dialysis machine likethe Fresenius Liberty© Cycler, which is not shown, controls the fill,dwell, and drain times of dialysate and monitors the dialysis process.Patient 210 receives clean dialysate from a container 212 connected tothe peritoneum cavity via a catheter or any other suitable access device211. Either on a continuous basis or after a period of dwell time, spentdialysate 201 is drained from patient 210 via a catheter or any othersuitable access device 211 to container 212. Container 212 can be one ormore containers. Spent dialysate 201 is sent through a cartridge 202containing materials to hydrolyze urea and remove phosphate and otherorganic uremic toxins. Spent dialysate 201 is then treated by anextractor system 209 to remove ammonia. As described above, theextractor system 209 includes a liquid-liquid countercurrent extractor203 and a heat cycler 205. Regenerated dialysate 208 exits the extractorsystem 209. Regenerated dialysate 208 can be returned to container 212to continue dialysis treatment.

The cartridge 202 can include a housing containing any suitable amountand type of materials to effectively hydrolyze urea in the dialysate andremove other toxins from the dialysate as it flows along the fluid path.The materials can be disposable such that, after use, the materials canbe removed from the housing and replaced with new materials. Thematerials can be in layers. The layers of material may include a urearemoval layer that includes urea-degrading enzymes, an organic uremictoxin removal layer that includes activated carbon, and/or an ionexchange layer that includes a phosphate binder or an ion exchangesorbent.

The cartridge can include the following layers and materials: sodiumzirconium carbonate or other alkali metal-Group IV metal-carbonate,alumina or other like material, alumina supported urease or otherimmobilized enzyme layer or other material to convert urea to ammonia,and granular activated carbon, such as charcoal or other absorbent.Sodium zirconium carbonate can act as a phosphate adsorbent. Zirconiumoxide or hydrous zirconium oxide can acts as a counter ion or ionexchanger to remove phosphate. Zirconium oxide and sodium zirconiumoxide can be in separate layers or can be blended together in the samelayer. The hydrous zirconium oxide can act as an anion exchange resin toremove phosphate.

Some examples of urea converting enzymes include naturally occurringenzymes, enzymes produced by recombinant technology, or syntheticallyproduced enzymes. The enzyme can be urease. The enzyme source can becross-linked jack bean meal.

Further examples of sorbent cartridges and suitable amounts forcartridge components are described in U.S. Pat. Nos. 6,627,164;6,878,283; 7,033,498; and 7,101,519, all incorporated in their entiretyby reference herein.

The present invention can further comprise a pump to move the fluidsthrough the system. The pump can be located before the sorbent cartridge102, 202. For example, a pump (not shown) can be located in a fluid flowpath between the spent dialysate outlet 116 and the sorbent cartridge102, or between the dialysate bag 212 and the sorbent cartridge 202,which can cause the dialysate fluid to move through the fluid circuitincluding the sorbent cartridge 102 (202), liquid-liquid counter currentseparator 103 (203), any supplemental sorbent cartridge 108, anddialyzer 111 (dialysate bag 212). The pump may be located at otherlocations in the fluid circuit, or multiple pumps at multiple locationsalong the fluid circuit may be used. The present invention can comprisea pump located after the heat cycler 105, 205 to move the fluid back tothe extractor 103, 203. For example, a pump (not shown) can be locatedin a fluid flow path between the heat cycler 105, 205 and theliquid-liquid counter current separator 103, 203 to move regeneratedextractant fluid from the heat cycler after ammonia expulsion back tothe separator.

The present invention can further comprise a chiller (not shown), suchas a cold water coil or constant temperature bath, located after theheat cycler 105, 205 and before the liquid-liquid countercurrentextractor 103, 203 to cool the solvent exiting the heat cycler 105, 205before returning it to the extractor.

The present invention can further comprise an ion exchange resin orother suitable device located before the liquid-liquid countercurrentextractor 103, 203 to increase the pH of the dialysis solution prior toentering the liquid-liquid countercurrent extractor 103, 203. Thepresent invention can further comprise a second ion exchange resin orother suitable device located after the liquid-liquid countercurrentextractor 103, 203 to lower the pH before returning the solution to thehemodialyzer 111 or the dialysate bag 212 connected to the patient 210.

As an option, none of the sorbent cartridges contain zirconiumphosphate. In other words, as an option, the present invention can beconducted without the presence or need for zirconium phosphate as one ofthe materials used in one or more of the cartridges. Zirconium phosphatecan have the formula Zr(HPO₄)₂.nH₂O. This can have significantadvantages in that zirconium phosphate can, in conventional cartridgesystems, comprise a large majority of the material used in a cartridge.Having the option and ability to avoid the use of zirconium phosphate orminimize the amount of zirconium phosphate can have numerous advantageswith regard to costs, size of cartridge, and other advantages.

The present invention further relates to a method of conductingdialysis, either hemodialysis or peritoneal dialysis, utilizing thesystem of the present invention, which includes a) at least one sorbentcartridge or other device that is capable of converting urea to ammoniaand carbon dioxide or to ammonium carbonate, and b) a liquid-liquidcounter-current extractor and a heater device, where the heater devicehas the ability to heat the solvent that contains one or more extractormolecules and ammonia so as to remove the ammonia due to the heating.The method can further include passing the dialysate, after ammoniaremoval, through one or more subsequent cartridges, for instance, one ormore cartridges that have the ability to remove phosphate and/or organicuremic toxins and/or other impurities.

The present invention includes the followingaspects/embodiments/features in any order and/or in any combination:

-   1. The present invention relates to a dialysis system comprising at    least one sorbent device and at least one liquid-liquid    counter-current extractor in fluid communication with said at least    one sorbent device, wherein said liquid-liquid counter-current    extractor comprises a) at least one liquid immiscible with a    dialysate solution and further comprises b) at least one extractor    molecule that is capable of removing ammonia from the dialysate    solution.-   2. The dialysis system of any preceding or following    embodiment/feature/aspect, further comprising at least one heater in    association with said at least one liquid-liquid extractor, wherein    said heater is capable of heating said at least one liquid and an    extractor molecule complexed with ammonia after said at least one    liquid and extractor molecule countercurrently passes spent    dialysate containing ammonia in said at least one liquid-liquid    extractor, to release ammonia from the complex and regenerate the    extractor molecule.-   3. The dialysis system of any preceding or following    embodiment/feature/aspect, wherein said at least sorbent device is    in fluid communication with a hemodialysis machine or peritoneal    dialysis machine to receive spent dialysate therefrom, and said    liquid-liquid counter-current extractor is in fluid communication    with said hemodialysis machine or peritoneal dialysis machine to    return regenerated dialysate thereto with or without one or more    additional sorbent devices fluidly connected therebetween.-   4. The dialysis system of any preceding or following    embodiment/feature/aspect, wherein said extractor molecule is a    cation exchange molecule.-   5. The dialysis system of any preceding or following    embodiment/feature/aspect, wherein said extractor molecule is a    phosphinic acid, a carboxylic acid, a phosphoric acid, or any    combination thereof.-   6. The dialysis system of any preceding or following    embodiment/feature/aspect, wherein said at least one liquid is    undecane, Norpar 12, a vegetable oil, a modified vegetable oil, a    biodiesel, or any combination thereof.-   7. The dialysis system of any preceding or following    embodiment/feature/aspect, wherein said sorbent device contains a    source of urease capable of converting urea to ammonia.-   8. The dialysis system of any preceding or following    embodiment/feature/aspect, wherein said source of urease is jack    bean meal, encapsulated jack bean meal, cross-linked jack bean meal    or other stabilized urease, or any combination thereof.-   9. The dialysis system of any preceding or following    embodiment/feature/aspect, wherein said source of urease is in the    form of one or more layers in a cartridge.-   10. The present invention is further directed to a method for    regenerating spent dialysate comprising passing said spent    dialysate, which contains urea, through at least one sorbent device    capable of converting at least a portion of said urea to ammonia,    and then passing said spent dialysate through a liquid-liquid    counter-current extractor to remove at least a portion of said    ammonia from said spent dialysate.-   11. The method of any preceding or following    embodiment/feature/aspect, further comprising passing said spent    dialysate, after removing at least a portion of said ammonia,    through one or more subsequent sorbent devices to further purify    said spent dialysate.-   12. The method of any preceding or following    embodiment/feature/aspect, wherein said one or more subsequent    sorbent devices comprise at least one cartridge capable of removing    phosphate or a portion thereof, and/or capable of removing organic    uremic toxins or a portion thereof.-   13. The method of any preceding or following    embodiment/feature/aspect, wherein said passing of said spent    dialysate through said liquid-liquid counter-current extractor    comprises countercurrently passing the spent dialysate containing    ammonia and at least one liquid immiscible with dialysate solution    containing an extractor molecule through said liquid-liquid    counter-current extractor, wherein the extractor molecule is    complexed with the ammonia removed from said spent dialysate to    produce a complex.-   14. The method of any preceding or following    embodiment/feature/aspect, further comprising heating said at least    one liquid and said complex after said countercurrently passing of    said spent dialysate and said at least one liquid, to break said    complex to release ammonia therefrom and regenerate the extractor    molecule.-   15. The method of any preceding or following    embodiment/feature/aspect, further comprising expelling said ammonia    from the liquid-liquid counter-current extractor after breaking said    complex, and returning said at least one liquid and regenerated    extractor molecule to said liquid-liquid counter-current extractor.-   16. The method of any preceding or following    embodiment/feature/aspect, wherein said extractor molecule is a    cation exchange molecule.-   17. The method of any preceding or following    embodiment/feature/aspect, wherein said extractor molecule is a    phosphinic acid, a carboxylic acid, a phosphoric acid, or any    combination thereof.-   18. The method of any preceding or following    embodiment/feature/aspect, wherein said at least one liquid is    undecane, Norpar 12, a vegetable oil, a modified vegetable oil, a    biodiesel, or any combination thereof.-   19. The method of any preceding or following    embodiment/feature/aspect, wherein said extractor molecule removes    from 95% to 100% by weight of all said ammonia from said spent    dialysate.-   20. The present invention further relates to a method for conducting    dialysis on a patient comprising the use of the dialysis system of    any preceding or following embodiment/feature/aspect, with a    hemodialysis machine or peritoneal dialysis machine.

The present invention can include any combination of these variousfeatures or embodiments above and/or below as set forth in sentencesand/or paragraphs. Any combination of disclosed features herein isconsidered part of the present invention and no limitation is intendedwith respect to combinable features.

Applicant specifically incorporates the entire contents of all citedreferences in this disclosure. Further, when an amount, concentration,or other value or parameter is given as either a range, preferred range,or a list of upper preferable values and lower preferable values, thisis to be understood as specifically disclosing all ranges formed fromany pair of any upper range limit or preferred value and any lower rangelimit or preferred value, regardless of whether ranges are separatelydisclosed. Where a range of numerical values is recited herein, unlessotherwise stated, the range is intended to include the endpointsthereof, and all integers and fractions within the range. It is notintended that the scope of the invention be limited to the specificvalues recited when defining a range.

Other embodiments of the present invention will be apparent to thoseskilled in the art from consideration of the present specification andpractice of the present invention disclosed herein. It is intended thatthe present specification and examples be considered as exemplary onlywith a true scope and spirit of the invention being indicated by thefollowing claims and equivalents thereof.

What is claimed is:
 1. A method for regenerating spent dialysatecomprising passing said spent dialysate, which contains urea, through atleast one sorbent device capable of converting at least a portion ofsaid urea to ammonia, and then passing said spent dialysate through aliquid-liquid counter-current extractor to remove at least a portion ofsaid ammonia from said spent dialysate, wherein said sorbent devicecontains a source containing urease that hydrolyzes urea to ammonia toform an ammonia-containing dialysate solution from spent dialysate, andwherein said liquid-liquid counter-current extractor comprises a) atleast one liquid immiscible with said ammonia-containing dialysatesolution, wherein the at least one liquid is an organic solvent, andfurther comprises b) at least one extractor molecule contained in theliquid that removes ammonia from said ammonia-containing dialysatesolution, wherein said ammonia-containing dialysate solution and said atleast one liquid immiscible solution containing said at least oneextractor molecule countercurrently pass through said liquid-liquidcounter-current extractor, and wherein said at least one sorbent deviceis in fluid communication with a hemodialysis machine or peritonealdialysis machine to receive said spent dialysate therefrom, and saidliquid-liquid counter-current extractor is in fluid communication withsaid hemodialysis machine or peritoneal dialysis machine, wherein saidliquid-liquid counter-current extractor produces regenerated dialysatethat is returned by the fluid communication to the hemodialysis machineor peritoneal dialysis machine.
 2. The method of claim 1, furthercomprising passing said spent dialysate, after removing at least aportion of said ammonia, through one or more subsequent sorbent devicesto further purify said spent dialysate.
 3. The method of claim 2,wherein said one or more subsequent sorbent devices comprise at leastone cartridge capable of removing phosphate or a portion thereof, and/orcapable of removing organic uremic toxins or a portion thereof.
 4. Themethod of claim 1, wherein said passing of said spent dialysate throughsaid liquid-liquid counter-current extractor comprises countercurrentlypassing the spent dialysate containing ammonia and at least one liquidimmiscible with dialysate solution containing an extractor moleculethrough said liquid-liquid counter-current extractor, wherein theextractor molecule is complexed with the ammonia removed from said spentdialysate to produce a complex.
 5. The method of claim 4, furthercomprising heating said at least one liquid and said complex after saidcountercurrently passing of said spent dialysate and said at least oneliquid, to break said complex to release ammonia therefrom andregenerate the extractor molecule.
 6. The method of claim 5, furthercomprising expelling said ammonia from the liquid-liquid counter-currentextractor after breaking said complex, and returning said at least oneliquid and regenerated extractor molecule to said liquid-liquidcounter-current extractor.
 7. The method of claim 4, wherein saidextractor molecule is a cation exchange molecule.
 8. The method of claim4, wherein said extractor molecule is a phosphinic acid, a carboxylicacid, a phosphoric acid, or any combination thereof.
 9. The method ofclaim 4, wherein said at least one liquid is undecane, Norpar 12, avegetable oil, a modified vegetable oil, a biodiesel, or any combinationthereof.
 10. The method of claim 4, wherein said extractor moleculeremoves from 95% to 100% by weight of all said ammonia from said spentdialysate.